目前认为脂质氧化在香烟诱导的COPD气道炎症中具有重要作用。近期的研究发现氧化型低密度脂蛋白（ox-LDL）及其受体LOX-1可能与香烟诱导的炎症反应密切相关。我们的前期研究发现，香烟暴露大鼠肺泡灌洗液、COPD患者血清中ox-LDL水平明显增高；体外研究进一步提示ox-LDL可刺激人气道上皮细胞产生炎症介质。我们推测ox-LDL/LOX-1可能参与了香烟诱导的COPD气道炎症反应。本研究拟通过构建香烟诱导的气道上皮细胞及小鼠气道炎症损伤模型，采用基因敲除，RNA干扰，特异性抑制剂等干预手段，探讨：1）ox-LDL/LOX-1信号通路在香烟诱导气道炎症中的作用机制，以及Rac1/Sirt1/NF-κB信号分子在其中的调控作用；2）探索基于ox-LDL/LOX-1治疗香烟诱导气道炎症的可行性，为COPD的治疗寻找新的靶点。

Lipid peroxidation plays an important role in cigarette smoke-induced airway inflammation in COPD. Recent studies suggested that ox-LDL, together with its receptor LOX-1, may be involved in cigarette smoke-induced inflammation. Our preliminary study revealed that ox-LDL levels in the bronchoaveolar lavage fluid of cigarette smoke-exposed rats and the serum of COPD patients were significant increased, in addition, ox-LDL also stimulated inflammatory mediator production in airway epithelial cells, which is involved in COPD. We speculated that the interaction of ox-LDL and LOX-1 play a role in cigarette smoke-induced airway inflammation. For present study, we plan to establish CSE/CS-induced inflammatory models in human bronchial epithelial cells and mouse airways, and use gene knockout mice, siRNA and specific inhibitor, to explore 1) the regulatory role of ox-LDL/LOX-1 in CS-induced airway inflammation, and the involvement of Rac1/Sirt1/NF-κB signals in LOX-1-mediated airway inflammation, and investigate 2）the effect of targeted intervention of LOX-1 and ox-LDL on CS-induced airway inflammation. This study is anticipated to offer the possibility to find a new therapeutic target of airway inflammation in COPD.